This program is concerned with the study of a variety of aspects of the biology and biochemistry of connective tissues. The following are the projects currently being actively pursued: 1) The structure of heparin and heparan sulfate, 2) The possible use of fractions of heparan sulfate and fragments derived from heparin for the prevention of arteriosclerosis, 3) The mechanism and control of biosynthesis of glycosaminoglycans, 4) The differentiation of limb-bud mesenchyme to cartilage including the mechanism by which the thymidine analogue, 5- bromo-2'-deoxyuridine, prevents such differentiation, 5) The effect of mechanical forces on the biosynthesis of glycosaminoglycans by smooth muscle cells, 6) The study of the underlying enzymic defects responsible for the mucopolysaccharidoses, 7) The study of the underlying defects responsible for glycoproteinoses and glycosphingolipidoses and 8) The mechanism and control biosynthesis of gangliosides in cultured cells derived from the nervous system including the specific effect of norepinephrine on ganglioside synthesis of neuroblastoma cells. Bibliographic references: Hyaluronic Acid Synthesis in a Cell-Free System from a Rat Firosarcoma. Hopwood, J.J. and Dorfman, A. Fed. Proc. 34, 565 (1975). Nature of the Collagen Synthesized by a Transplanted Chondrosarcoma. Smith, B. D., Martin, G. R., Miller, E. J., Dorfman, A. and Swarm, R. Archiv. Biochem. Biophys. 166, 181-186 (1975).